The Role of Macrophages in Early Healing of a Tendon Graft in a Bone Tunnel

Hays, Peyton L.; Kawamura, Syosuke; Deng, Xiang‐Hua; Dagher, Elias; Mithoefer, Kai; Liang, Ying; Rodeo, Scott A.

doi:10.2106/jbjs.f.00531

Cited by 155 publications

(145 citation statements)

References 45 publications

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“…effect of alendronate on tunnel and peri-tunnel bone and week 2-ultimate load and the effect was most marked at the tibial tunnel metaphysis. The effects of alendronate on the improvement of tendon graft to bone tunnel healing were consistent with the results of Thomopoulos et al (2007) and Hays et al (2008). Bisphosphonate was reported to suppress bone loss and improved tendonto-bone repair strength in a flexor tendon canine model (Thomopoulos et al, 2007).…”

Section: Fig 11supporting

confidence: 86%

“…Alendronate has been reported to suppress bone loss and improve tendonto-bone repair strength in a flexor tendon canine model (Thomopoulos et al, 2007). In another study, clodronate was reported to induce macrophage apoptosis and promote tendon graft to bone tunnel healing (Hays et al, 2008). The first study was not an ACL reconstruction model and the second study used the non-nitrogen-containing bisphosphonate, which has different mechanisms of action compared to nitrogen-containing bisphosphonate.…”

Section: Introductionmentioning

confidence: 99%

“…The first study was not an ACL reconstruction model and the second study used the non-nitrogen-containing bisphosphonate, which has different mechanisms of action compared to nitrogen-containing bisphosphonate. The effect of clodronate on the peri-tunnel bone was not studied (Hays et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Alendronate reduced peri-tunnel bone loss and enhanced tendon graft to bone tunnel healing in anterior cruciate ligament reconstruction

Lui

Lee²,

Mok³

et al. 2013

eCM

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Peri-tunnel bone loss after anterior cruciate ligament (ACL) reconstruction is commonly observed, both clinically and experimentally. We aimed to study the effect and mechanisms of different doses of alendronate in the reduction of peritunnel bone loss and promotion of graft-bone tunnel healing in ACL reconstruction. Eighty-four ACL-reconstructed rats were divided into 4 groups. Alendronate at different dosages, or saline, were injected subcutaneously weekly, for 2 or 6 weeks post-reconstruction, for vivaCT (computed tomography) imaging, biomechanical tests, histology and immunohistochemistry. Alendronate significantly increased bone mass and density of tissue inside bone tunnels except at the epiphyseal region of tibial tunnel. The femoral tunnel diameter decreased significantly in the mid-dose and highdose alendronate groups compared to that in the saline group at week 6. Alendronate significantly increased the peri-tunnel bone mass and density along all tunnel regions at week 6. Better graft-bone tunnel integration and intra-tunnel graft integrity were observed in the alendronate groups. The ultimate load was significantly higher in the mid-dose and high-dose alendronate groups at week 2, but not at week 6. There was a reduction in matrix metalloprotein (MMP)1, MMP13 and CD68-positive cells at the peri-tunnel region and graft-bone interface in the alendronate-treated group compared to the saline group. Alendronate reduced peritunnel bone resorption, increased mineralised tissue inside bone tunnel as well as histologically and biomechanically promoted graft-bone tunnel healing, probably by reducing the expression of MMP1, MMP13 and CD68-positive cells. Alendronate might be used for reducing peri-tunnel bone loss and promoting graft-bone tunnel healing at early stage post-ACL reconstruction.

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Section: Fig 11supporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Alendronate reduced peri-tunnel bone loss and enhanced tendon graft to bone tunnel healing in anterior cruciate ligament reconstruction

Lui

Lee²,

Mok³

et al. 2013

eCM

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“…The inflammatory stage begins within the first week of rotator cuff repair and is characterized by the infiltration of neutrophils and recruited macrophages. These recruited macrophages secrete transforming growth factor b1 (TGFb1), which increases proteinase activity and collagen formation [26]. These early-recruited macrophages contribute to the formation of fibrovascular scar tissue; it is likely TGF-b1 secretion is the mechanism of scar tissue formation in the presence of recruited macrophages.…”

Section: Biology Of Bone-to-tendon Healingmentioning

confidence: 99%

“…These early-recruited macrophages contribute to the formation of fibrovascular scar tissue; it is likely TGF-b1 secretion is the mechanism of scar tissue formation in the presence of recruited macrophages. Local macrophages are also present in smaller numbers in the repairing bone-to-tendon insertion point; local macrophages are thought to have a positive anabolic function opposed to the catabolic function observed in the recruited macrophages [26]. Additionally, inflammation occurs after tendon overuse injuries and may serve as a protective mechanism in this setting [43].…”

Section: Biology Of Bone-to-tendon Healingmentioning

confidence: 99%

Strategies in Biologic Augmentation of Rotator Cuff Repair: A Review

Cheung

Silverio

Sperling

2010

Clinical Orthopaedics &Amp; Related Research

146

103

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Background Degenerative rotator cuff tears are increasing with the aging population, and healing is not uniform after surgery. Rotator cuffs may show improved healing when biologic factors are added during surgery. Questions/purposes We asked: (1) What cellular processes are involved in normal bone-to-tendon healing? (2) What approaches are being developed in tendon augmentation? (3) What approaches are being developed with the addition of growth factors? Methods We reviewed research in relating to biologic augmentation and cellular processes involved in rotator cuff repair, focusing on animal models of rotator cuff repair and nonrandomized human trials. Results Regular bone-to-tendon healing forms a fibrous junction between tendon and bone that is distinct from the original bone-to-tendon junction. Tendon augmentation with cellular components serves as scaffolding for fibroblastic cells and a possible source of growth factors and fibroblastic cells. Extracellular matrices provide a scaffold for incoming fibroblastic cells, although current research does not conclusively confirm which if any of these scaffolds enhance repair owing in part to intermanufacturer variations and the limited human research. Growth factors and platelet-rich-plasma are established in other fields of research and may enhance repair but have not been rigorously tested. Conclusions There is potential application of biologic augmentation to improve healing after rotator cuff repair. However, research in this field is still inconclusive and has not been sufficiently demonstrated to merit regular clinical use. Future human trials can elucidate the use of biologic augmentation in rotator cuff repairs.

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Injectable bioactive glass/sodium alginate hydrogel with immunomodulatory and angiogenic properties for enhanced tendon healing

Zhu

et al. 2022

Bioengineering & Transla Med

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Tendon healing is a complex process involving inflammation, proliferation, and remodeling, eventually achieving a state of hypocellularity and hypovascularity. Currently, few treatments can satisfactorily restore the structure and function of native tendon. Bioactive glass (BG) has been shown to possess immunomodulatory and angiogenic properties. In this study, we investigated whether an injectable hydrogel fabricated of BG and sodium alginate (SA) could be applied to enhance tenogenesis following suture repair of injured tendon. We demonstrated that BG/SA hydrogel significantly accelerated tenogenesis without inducing heterotopic ossification based on histological analysis. The therapeutic effect could attribute to increased angiogenesis and M1 to M2 phenotypic switch of macrophages within 7 days post‐surgery. Morphological characterization demonstrated that BG/SA hydrogel partially reverted the pathological changes of Achilles tendon, including increased length and cross‐sectional area (CSA). Finally, biomechanical test showed that BG/SA hydrogel significantly improved ultimate load, failure stress, and tensile modulus of the repaired tendon. In conclusion, administration of an injectable BG/SA hydrogel can be a novel and promising therapeutic approach to augment Achilles tendon healing in conjunction with surgical intervention.

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The Role of Macrophages in Early Healing of a Tendon Graft in a Bone Tunnel

Abstract: Macrophage depletion following anterior cruciate ligament reconstruction resulted in significantly improved morphologic and biomechanical properties at the healing tendon-bone interface, which we hypothesize are due to diminished macrophage-induced TGF-beta production.

Cited by 155 publications

References 45 publications

Alendronate reduced peri-tunnel bone loss and enhanced tendon graft to bone tunnel healing in anterior cruciate ligament reconstruction

Alendronate reduced peri-tunnel bone loss and enhanced tendon graft to bone tunnel healing in anterior cruciate ligament reconstruction

Strategies in Biologic Augmentation of Rotator Cuff Repair: A Review

Injectable bioactive glass/sodium alginate hydrogel with immunomodulatory and angiogenic properties for enhanced tendon healing

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